Methods Forty-two consecutive patients, 35 of whom had implantable cardioverter-defibrillator, all referred for VT RFCA, underwent pre-procedural CT including an angiographic and a 10-min delayed-enhancement scan. Segmental comparison between scars segmented from CT and low voltages (bipolar voltages <1.5 mV; unipolar voltages <8 mV), late potentials, and RF ablation points on EAM, was carried out. In a subset of 16 consecutive patients, a further point-by-point analysis was performed: a CT-derived 3-dimensional structure including heart anatomy and myocardial scars was integrated with EAM for quantitative comparison.

Results CT scans identified scars in 39 patients and defined left ventricular wall involvement and mural distribution. Overall segmental concordance between CT and EAM was good (κ = 0.536) despite the presence of implantable cardioverter-defibrillator, scar etiologies, and mural distribution. CT identified segments characterized by low voltages with good sensitivity (76%), good specificity (86%), and very high negative predictive value (95%). Late potentials and RF ablation points fell on scarred segments identified from CT in 79% and 81% of cases, respectively. Point-by-point quantitative comparison revealed good correlation between the average area of scar detected at CT and at bipolar mapping (CT = 4,901 mm2, bipolar voltages-EAM = 4,070 mm2; R = 0.78; p < 0.0001). In this study, 70% and 84% of low-amplitude bipolar points were mapped at a maximum distance of 5 mm and 10 mm from CT-segmented scar, respectively.

Conclusions CT with delayed-enhancement provides a 3-dimensional characterization of VT scar substrate together with a detailed anatomic model of the heart. This information may offer assistance to plan EAM and RFCA procedures and is potentially suitable for EAM-imaging integration.

Ventricular tachycardia (VT) is a life-threatening arrhythmia, frequently based on a scar substrate of ischemic and nonischemic origin. Patients with scar-related VT are subject to arrhythmia recurrence that is poorly controlled by chronic pharmacological therapies. The implantable cardioverter-defibrillator (ICD) is a life preserver but it is noncurative and therefore ICD-implanted patients may experience severe impairment in their quality-of-life due to recurrent ICD shocks. Radiofrequency catheter ablation (RFCA) is the only curative option for most patients, both with and without ICD.

Electro-anatomic mapping (EAM) is commonly used for mapping VT substrate to guide RFCA. EAM are created by combining cardiac surface electrical activation recorded by catheter contact, with the spatial location of the catheter tip, in order to identify myocardial scars as areas of low bipolar voltages (BV) or unipolar voltages (UV) (1). Despite the fact that EAM is the current standard for guiding the substrate-based RFCA, it remains a very time-consuming and challenging procedure, with some drawbacks such as limited spatial resolution and the inaccurate delineation of intramural scars (2). These limitations infer the development of image integration strategies for RFCA. Several studies have already explored the integration of the delayed-enhancement cardiac magnetic resonance (DE-CMR) (3–6). DE-CMR can accurately visualize scars, but its integration with EAM is strongly limited by the presence of ICD in the majority of patients undergoing RFCA. If appropriate safety measures are taken, ICD presence may not necessarily preclude CMR, but a detailed evaluation of a large part of the left ventricle (LV) is hampered by artifacts related to the ICD’s pulse generator (7,8). Moreover, whole-heart coverage with isotropic resolution is still challenging in DE-CMR.

In this study, we propose the use of computed tomography (CT) with delayed-enhancement imaging (CTDE) for myocardial scar identification in patients referred for RFCA of VT. The specific aim was to compare anatomic and structural information obtained from a pre-procedural CT study that included both computed tomography angiography (CTA) and CTDE scan, with electrical features of EAM, in order to assess the potential role of CT integration in VT-RFCA procedures.

Methods

This study was approved by the institutional review board (GR-2009-1594705) and all patients provided signed informed consent.

CT and EAM were compared on a segment-by-segment basis. In 16 consecutive patients, a 3-dimensional (3D) structure obtained by the fusion of segmented CTA and CTDE was uploaded onto the CARTO system (Biosense Webster, South Diamond Bar, California) and a further point-by-point quantitative comparison was obtained.

Cardiac-CT protocol

Patients with heart rate >65 beats/min were prepared with intravenous beta-blockers (atenolol 1 to 15 mg), in the absence of any major contraindications. In 3 patients, CT was performed during continuous intravenous infusion of lidocaine hydrochloride to control ventricular arrhythmias.

Electro-anatomic mapping and ablation procedure

Endocardial maps were obtained for all patients and an additional epicardial map in 21 cases. High-density maps of the entire LV were obtained using the CARTO magnetic mapping system with the Navistar Thermocool Smart Touch catheter (Biosense Webster) in 30 of 42 patients (threshold force 8g) and the Navistar Thermocool SF catheter (Biosense Webster) in 12 of 42 patients. In order to achieve homogeneously detailed maps, the fill threshold was set to 10 mm in areas with normal voltages and to 5 mm in areas with low-voltage amplitude. Normal LV BV was defined as a value higher than 1.5 mV, and normal LV UV was defined as a value higher than 8 mV (3). Late potential (LP) were defined as continuous fragmented activity or isolated potentials recorded after the QRS complex. RFCA was performed using an irrigated-tip catheter, with a power setting of 30 to 50 W at temperatures up to a maximum of 43°C (irrigation flow was set at 17 and 30 ml/min in accordance with the power setting).

The endpoints of the procedure were suppression of induced clinical VT and/or disappearance of delayed components in those patients with unmappable VT (3,10).

Quantitative assessment of ICD-related artifacts

The percentage of myocardium involved by ICD-related streak artifacts was quantified in both CTA and CTDE images, after LV wall semiautomatic segmentation, quantifying voxels with values higher than 20% of the maximum density (hyperdense artifact) (11) and below an empirical threshold of –150 Hounsfield units (HU) (hypodense artifacts).

Segmental analysis of CT images and EAM

A segmental analysis of CT and EAM was performed in all patients, according to the 17 LV segments classification of the American Heart Association. Areas of wall thickness <5 mm, or wall thinning (WTN), were identified using CTA images. Presence and transmurality (subendocardial, mesocardial, subepicardial, and transmural) of DE were defined visually, together with the CTDE scan image quality (1 = good, 2 = sufficient, 3 = not assessable). All DE areas were considered as scar; moreover, areas of WTN associated with LV bulging or aneurismatic dilation were also defined as scar. Two readers with 4 and 11 years of experience in cardiac imaging defined the presence and mural distribution of scar. Interobserver concordance was assessed according to a 3-point scale (1 = sure scar, 2 = probable scar, 3 = absence of scar). Any interobserver disagreements were resolved by consensus. HU of normal myocardium and DE areas were measured. An experienced arrhythmologist (G.M., F.B., P.D.B.), blinded to the results of CT, defined the segmental distribution of scar areas at EAM, of LP, and of RFCA sites.

Quantitative 3D CT and EAM analysis

In the last 16 consecutive patients enrolled, coronary arteries, LV wall, cardiac chambers and scars, recognized according to previously described criteria, were semiautomatically segmented (Extended Brilliance Workspace, Philips Medical System) using CTA and CTDE scans. CTA was used as the reference volume for coregistration of CTA and CTDE scans; mutual information as a similarity measure was applied in order to deal with differences in myocardial density (12). After a rigid registration, an additional elastic registration using a B-spline interpolator (13) was performed to reduce the effects linked to the heart’s motion. The obtained 3D structure was exported into DICOM (Digital Imagine and Communications in Medicine) format and uploaded on CARTO; in particular, the surface of the aortic and LV maps were automatically aligned with the meshes using CartoMERGE software (Biosense Webster). The match between all mapping points and scar at CT was performed. Contours were processed by VTK software toolkit (Kitware, Clifton Park, New York) to generate EAM points surface and CT scar volume. CT-defined scar was projected over EAM surface to assess corresponding voltages; the percentage of pathological voltages within a maximum distance of 5 and 10 mm from CT scar was calculated.

Statistical analysis

Sensitivity, specificity, positive predictive value and negative predictive value of CT in prediction of scar at EAM were calculated, taking into consideration all segments (714 segments; 21% with scar) and also excluding segments with scar prevalence <20% to reduce impact of low prevalence (252 segments; 31% with scar). A Cohen kappa coefficient (κ), with correction for indeterminacy (14), was calculated to assess interobserver agreement and to evaluate the concordance between CT and EAM features (<0.20: poor; 0.20 to 0.40: fair; 0.40 to 0.60: moderate; 0.60 to 0.80: good; 0.80 to 1.00: very good agreement). All measures were reported averaged over segments. Logistic or ordered logistic regression models were estimated using the backward selection procedure to evaluate which covariates predict low segmental quality, and Poisson regression was used for the number of nonassessable segments. Two-sample Student t test was used to measure the difference between means and the Pearson coefficient–measured correlation. p Values <0.05 were considered statistically significant. Statistical analyses were performed using R version 3.0.2 (R Foundation, Vienna, Austria) and SPSS software version 16.0 (SPSS Inc., Armonk, New York).

Results

Baseline characteristics of patient population are reported in Table 1. CT including both CTA and CTDE was completed in 41 patients; 1 patient underwent only CTA because of limited cooperation. RFCA was performed in 41 patients because VT was not inducible in 1.

Myocardial scars at CT

Myocardial scars were detected at CT in 39 patients, with an average involvement of 4.6 ± 2.2 myocardial segments. A good interobserver agreement in scar detection at CT was found (κ = 0.697). Basal anterolateral, inferolateral, and inferior segments, as well as inferolateral medium segment, were the most frequently involved (in 45%, 61%, 50%, and 47% of patients, respectively). In 36 patients, myocardial scars were identified by the presence of DE and, in 27 of them, DE was associated with WTN. In the remaining 3 patients, myocardial scars were only identified by the presence of WTN associated with local bulging or aneurysms: CTDE was not performed in 1 patient, whereas a low-image quality prevented an accurate assessment of DE of thinned wall in the remaining 2 patients. DE alone involved 4.9 ± 2.5 LV segments and showed the following parietal distribution: subendocardial in 13 of 36, mesocardial in 1 of 36, subepicardial in 7 of 36, and transmural in 15 of 36 patients. WTN alone involved 3.8 ± 2.3 segments and most patients with WTN suffered from ICM (67%, 20 of 30). WTN and DE showed a moderate agreement (κ = 0.564), higher in ICM than in NICM patients (κ = 0.585 vs. κ = 0.458, respectively). Areas of DE were characterized by higher mean attenuation values than normal myocardium (281 ± 39 HU vs. 202 ± 42 HU; p < 0.0001), without significant differences between ICM and NICM patients (275 ± 39 HU vs. 196 ± 43 HU and 289 ± 39 HU vs. 209 ± 41 HU, respectively).

EAM and RFCA

The average number of mapping points was 450 ± 251 and 547 ± 282 for endocardial and epicardial EAM, respectively. Low voltages suggestive of scar were identified in 40 patients, with an average involvement of 3.7 ± 2.0 segments. In 23 patients, scars were identified upon endocardial mapping, in 10 patients in both endocardial and epicardial maps, and in 7 patients in epicardial maps only. LP were identified in 38 patients with an average involvement of 2.5 ± 1.3 segments. VT targets were identified and ablated in 41 patients. One patient without evidence of low pathological voltages had VT target in the LP sites. RFCA was performed on the endocardium in 31 patients, on the epicardium in 5 patients, and on both endocardium and epicardium in 5 patients. Mean number of LV segments involved by RFCA was 2.4 ± 1.0.

RFCA was completely successful in 88% of patients (36 to 41) without the induction of arrhythmic events at the end of the procedure. In 4 of 41 patients, RFCA resulted in a partial success, with the elimination of the clinical VT but persistent inducibility of nonclinical VT. In a single case, the procedure failed with persistent inducibility of the clinical VT. Eleven patients (27%) had recurrence of VT during the first year after ablation.

Segmental comparison between scars at CT and low voltages at EAM

CT and EAM showed a good overall concordance (κ = 0.536) in the detection of scar, regardless of scar etiologies, transmural distribution of scar at imaging, EAM approach (endocardial/epicardial), and voltages (BV/UV) used (Figures 2 and 3). Table 2 shows detailed results of segmental agreement between scars with different mural distribution at CT and areas of pathological BV or UV at EAM; the agreement varied from moderate to very good. As expected in patients with subepicardial scar at imaging, a closer agreement with epicardial than endocardial map was found and, in this case, the agreement was higher when UV were recorded. Similarly, in case of scar with mesocardial pattern at CT, the agreement was higher with UV than BV.

Short-axis (left→right = base→apex) and long-axis views of computed tomography angiography and computed tomography delayed enhancement scans are reported in A and B, respectively. Delayed enhancement (DE) images (B) show a large area of inhomogeneous wall hyperdensity with a prevalent subepicardial distribution in the lateral wall, referable to a nonischemic scar. A further small DE area with mesocardial-subepicardial distribution is evident in the anterior basal septum (B). Areas of DE are represented in pink in the CT 3-dimensional model of the heart (C,D). A good agreement was found between CT-segmented scar (C,D) and pathological voltages at EAM (E to H). Interestingly, endocardial unipolar EAM (E,F,H) identify the thickest part of the scar detected by CT. A very good match was found between CT (C,D) and epicardial bipolar EAM (G). NICM = nonischemic dilated cardiomyopathy; other abbreviations as in Figure 2.

Diagnostic performance of CT

Considering the scar defined at EAM as the reference standard, CT demonstrated a sensitivity of 76% and a specificity of 86% in the detection of scar, with limited positive predictive value (56%) and very high negative predictive value (95%). Sensitivity, specificity, positive predictive value, and negative predictive value were 84%, 88%, 80%, and 93%, respectively, when analysis was restricted to segments with prevalence of scar higher than 20% (Table 3). Results regarding the diagnostic performance of the single CT parameters (DE and WTN) are reported in Table 3.

Diagnostic Performance of CT in the Detection of Myocardial Substrate of VT, as Identified at EAM

Relationship between CT-defined scar and LP–RFCA targets

LP completely matched with segmental distribution of scar at CT in 79% of patients (30 of 38), a partial match was found in 10.5% (4 of 38) and no match in the remaining 4 patients. Similar results were found for RFCA points: a complete match in 81% (33 of 41), a partial match in 7% (3 of 41), and an absent match in 12% (5 of 41).

CT-defined scar (magenta) was superimposed to EAM (color-mapped points) (A). All EAM points under CT-segmented scar were identified (B). The distance between all points with low voltages (orange) to the nearest CT-defined scar was assessed (C), and the percentage of low-voltage points within 5 and 10 mm calculated. Abbreviations as in Figure 2.

Discussion

Noninvasive imaging for the 3D characterization of VT substrate is helpful in the planning and guidance of RFCA, integrating detailed anatomic and structural information. The integration of CT images into EAM systems is today a common approach in the RFCA of atrial fibrillation, where 3D imaging datasets guide catheter mapping on the basis of individual atrial and pulmonary vein anatomy (15).

In the RFCA of nonidiopathic VT, success depends on the ability to release RF on myocardial scars, hence a pure anatomic support has limited usefulness. DE-CMR was largely proposed for pre-procedural scar identification and subsequent intraprocedural registration with the EAM (16). Although DE-CMR is the standard of reference for myocardial scar depiction and has been shown to be accurate for detection and characterization of ventricular arrhythmia substrate (5,17), its application is limited in patients with ICD, due to the strong artifacts created by the presence of the ICD’s generator (8). This is a major problem for imaging of VT substrate because at least 70% of patients referred for VT RFCA have an ICD (18). In selected patients without ICD, scars segmented from DE-CMR showed good correlation with low voltages detected at EAM both in patients with previous myocardial infarction (16,17,19) and in patients with post-myocarditis scars (20). In particular, in patients with ICM, Cohen κ coefficients between the CMR-defined and EAM-defined scar in the range 0.36 (reference 19) to 0.7 (reference 17) were reported. The Cohen κ coefficient found in our study (κ = 0.536) was exactly in the middle of this range, suggesting similar performances for DE-CMR and CTDE, although in our analysis both ICM and NICM patients, as well as patients with and without ICD, were included. Conversely, a previous DE-CMR study performed in patients with ICD demonstrated unsatisfactory results, with only 9 ± 4 of the 17 LV segments fully assessable, due to the presence of important hyperintensity artifacts that were most prominent in the anterior wall (7). A novel wideband DE-CMR technique was recently developed to reduce the artifacts related to the ICD’s generator and represents a promising approach to increase the use of CMR for the characterization of arrhythmia substrates, although this technique is not yet widely available and needs further validation (21).

In this study, we detected myocardial scars responsible for low-amplitude voltages at EAM with high sensitivity and very high negative predictive values, regardless of the presence of ICD, using a double-phase CT protocol. Streaks artifacts linked to ICD electrocatheters involve only around 1% of the LV wall, having an impact on the assessability of only 2 segments. A further advantage of CT is the acquisition of the whole heart in few seconds with high 3D isotropic resolution, which is essential for imaging integration with EAM and for detailed scar depiction (5). A single previous study proposed the use of CT-derived scar for integration into clinical EAM. Differently from our work, Tian et al. (22) defined the presence and location of scar on the basis of anatomic and functional parameters (wall thickness, wall thickening, wall motion, and CT evidence of hypoperfusion), without using CTDE. They studied 11 patients with ICM, obtaining promising results, although only 40% of LV segments were completely analyzed. Moreover, although the proposed approach may have a rationale in ICM patients, it may fail in the identification of NICM scars (20). We proposed the use of CTDE because different published data evidence suggested good accuracy in the identification of both ischemic and nonischemic scars (23–25), also compared to DE-CMR (23).

Our results demonstrated concordance between VT substrate detected by CT and low-voltage area at EAM, regardless of the substrate etiology. CT allows identifying areas characterized by pathological voltages at EAM, with CTDE dramatically superior to WTN in terms of sensitivity. Moreover, CTDE guarantees very high negative predictive values, suggesting a low probability of finding pathological voltages outside scar defined at CT. CTDE also defines and depicts the intramural distribution of the scar, a very important aspect in guiding the choice of best EAM approach and voltages for each patient.

The point-by-point analysis revealed good correlation between the scar extension at CT and the extension of low BV; lower was the correlation between CT-defined scar area and low-UV area, probably due to the known lower specificity of UV-EAM. Accordingly, most of low-amplitude BV points resulted within a maximum distance of 10 mm from the CT-segmented scar, further suggesting that CT integration may facilitate focusing the mapping process. This was also supported by the high percentage of LP and RFCA points matching with the areas of scar at CT.

Study limitations

The main limitation of CTDE is the relatively low contrast-to-noise ratio when compared with DE-CMR. This limited contrast-to-noise ratio influences the possibility of automating the post-processing, which should be semiautomatically performed by an experienced operator on a commercial post-processing package, for scar segmentation. Moreover, limitation in contrast resolution of CTDE images may obstruct a clear distinction between the “dense core” of the scar and the “gray zone,” where the conducting channels responsible for re-entrant circuits are more frequently found (5). Nonetheless, in our study, using voltage cutoffs that include both the dense scar and the gray zone, most pathological voltages resulted within or very close to the CT-segmented scar, suggesting that both the scar components are included in our CT-based segmentation. Furthermore, in the near future, the diffusion of new-generation CT scanners may significantly improve the possibility of CTDE scar characterization. Several hardware and software developments promise to minimize image noise, and the introduction of cardiac spectral CT imaging provides an opportunity to obtain delayed iodine myocardial maps that could represent the future of CTDE imaging.

Conclusions

This is the first study to assess the spatial agreement between the myocardial scars defined with a double-phase CT protocol and electro-anatomic features in patients submitted to RFCA of recurrent VT. These early results highlight the potential value of this approach in the planning, which may assist the performance of EAM and RFCA process. Future randomized prospective studies are required to evaluate the impact on procedural time and patient’s outcome.

Perspectives

COMPETENCY IN MEDICAL KNOWLEDGE: Cardiac CT with DE technique provides a 3D depiction of structural substrate at the VT origin, together with a detailed heart anatomy, regardless of the presence of ICD. Pre-procedural cardiac CT imaging helps in the planning of EAM and RFCA in patients with VT. Moreover, a CT-derived 3D structure including segmentation of coronary arteries, LV wall, cardiac chambers and scars that is suitable for image integration on CARTO may directly guide the arrhythmologist toward the areas of pathological voltages.

TRANSLATIONAL OUTLOOK: The subjectivity of the visually based segmentation of scar remains a limitation of the proposed approach; however, the increase in the contrast-to-noise ratio allowed by the new-generation CT scanners, as well as the introduction of cardiac spectral CT imaging, promise to improve scar detection and to increase the possibility of standardized automatic scar segmentation. Nevertheless, future randomized prospective studies are required to evaluate the impact of CT images integration on procedural time and patients’ outcome.

Footnotes

This research was partially supported by a grant from the Italian Ministry of Health: “Giovani Ricercatori—Ricerca Finalizzata,” project number GR-2009-1594705. The funders had no role in this study. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Dr. Maccabelli is deceased.